Name: sample extraction and simultaneous chromatographic quantitation of doxorubicin and mitomycin c following drug combination delivery in nanoparticles to tumor-bearing mice
Uploaded: 2017-10-05T13:00:00
Description: Watch this Scientific Journal Video about Sample Extraction and Simultaneous Chromatographic Quantitation of Doxorubicin and Mitomycin C Following Drug Combination Delivery in Nanoparticles to Tumor-b

作者衷心感谢加拿大自然科学与工程研究理事会 ( NSERC ) 为高效液相色谱 , 加拿大卫生研究院 ( 研究院 ) 和加拿腺癌研究 ( CBCR ) 提供的手术补助金。加盟 x.y.z 吴, 和多伦多大学奖学金 R.X. 张和 t。

所有动物实验均由安大略省癌症研究所的大学卫生网络动物保育委员会批准, 并按照加拿大动物保育理事会的准则进行. 
 1. 生物样品制备 <ol> <li> 在静脉注射 (静脉注射) 药物制剂后, 在预定的时点上收集全血、主要脏器和乳腺肿瘤 (如 ,DMPLN, 脂质体 DOX) <ol> <li> 用准备好的含药物的制剂注射乳房肿瘤的小鼠静脉注射. </li>
		<li> 麻醉在指定的时点 ( 如 , 1...

与其他能同时检测单一药物种类的色谱方法相比, 目前的 HPLC 协议能够同时定量三药物化合物 (DOX、MMC 和 DOXol) 在同一生物基质中, 无需改变移动阶段。这种制备和分析方法已成功地应用于确定两个纳米药物传递系统 (即脂质体 DOX 和 DMPLN) 的药代动力学和生物分布,22。由于乙二醇纳米颗粒可延长负载药物的全身循环, 从而在很长一段时间 (#62; 24 h) 中产生高血药浓度, ?...

化疗是许多癌症的主要治疗方式, 但它往往与严重的副作用和有限的功效, 由于耐药性和其他因素1,2,3。为了改善化疗的结果, 药物组合方案已在临床应用的考虑因素, 如不重叠的毒性, 不同的药物作用机制, 和非耐药性4,5,6. 在临床试验中, 与序贯药物传递的方案相比, 经常观察到肿瘤的反应率更高, 其方法是:7,8。然而, 由于游离药物形态的非最佳生物分布, 同时注射多种药物可引起明显的正常组织毒性, 超过治疗效果9,10,11。Nanocarrier-based 药物的传递已被证明改变药代动力学和生物分布的封装药物, 加强肿瘤靶向积累12,13,14。正如我们在最近的文章中所回顾的, 与协同药物组合的纳米 co-loaded 已经证明了能够减轻自由药物组合所遇到的问题, 由于其控制的时间和空间 co-delivery多种药物对肿瘤组织, 使协同药物对癌细胞的作用4,15,16。结果, 在临床前和临床医学研究中均表现出优异的治疗效果和低毒力4,17,18。
我们以前的体外研究发现, 两种抗癌药物, 阿霉素 (DOX) 和丝裂霉 C (mmc) 的结合, 产生了对几个乳腺癌细胞株的协同作用, 此外, co-loading DOX 和 mmc 在聚合物-脂质混合纳米颗粒 (DMPLN) 克服了各种耐药相关的外排泵 (例如, p-糖蛋白和抗乳腺癌蛋白)19,20,21。在体内, DMPLN 使 DOX 和 MMC 的空间颞 co-delivery 对肿瘤部位和癌症细胞内药物的生物利用度提高, 这表明 DOX 代谢产物 doxorubicinol (DOXol)22的形成是适度的。结果, DMPLN 增强肿瘤细胞凋亡, 抑制肿瘤生长, 延长宿主存活率, 与游离 DOX 和 MMC 组合物或脂质体 DOX 配方22,23,24, 25。
分析 nanocarrier co-delivered 药物的实际用量对于设计有效的纳米粒子配方是至关重要的。采用高效液相色谱 (HPLC) 单独或与质谱联用 (MS)26、27、28等方法, 对单 DOX 或 MMC 剂量的血浆水平进行了分析。,29,30,31,32,33,34. 然而, 这些方法往往是费时和不切实际的组合疗法, 因为大量的生物样品需要单独准备的分析多种药物 (有时包括药物代谢物)。除了强的血浆蛋白结合 DOX 和 MMC, 红细胞也有很大的能力绑定和集中许多抗癌药物35,36。因此, DOX 或 MMC 的等离子分析可能会混淆实际的血药浓度。本工作 (图 1) 描述了一种简单而稳健的多药分析方法, 采用反相高效液相色谱法同时提取和定量 DOX、MMC 和 DOX 代谢物 doxorubicinol (DOXol) 的全血和各种组织 (例如,肿瘤)。它已成功地应用于确定药物的药代动力学和生物分布的 DOX 和 MMC, 以及形成的 DOXol 后, 通过免费的解决方案或纳米颗粒 (即, DMPLN 和脂质体 DOX) 在原位植入小鼠乳腺肿瘤模型静脉注射后 (静脉注射)22。

<table style="border-collapse:collapse;width:635pt" width="846">
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		<col style="width:188pt" width="250" />
		<col style="width:122pt" width="162" />
		<col style="width:89pt" width="119" />
		<col style="width:236pt" width="315" />
	</colgroup>
	<tbody>
		<tr height="21" style="height:15.75pt">
			<td class="xl20" height="21" style="width:188pt;height:15.75pt" width="250">Doxorubicin&#160;</td>
			<td class="xl20" style="width:122pt" width="162">Polymed Theraeutics</td>
			<td class="xl20" style="width:89pt" width="119">111023</td>
			<td class="xl20" style="width:236pt" width="315">Anticancer drug</td>
		</tr>
		<tr height="21" style="height:15.75pt">
			<td class="xl20" height="21" style="width:188pt;height:15.75pt" width="250">Mitomycin C</td>
			<td class="xl20" style="width:122pt" width="162">Polymed Theraeutics</td>
			<td class="xl20" style="width:89pt" width="119">060814</td>
			<td class="xl20" style="width:236pt" width="315">Anticancer drug</td>
		</tr>
		<tr height="42" style="height:31.5pt">
			<td class="xl20" height="42" style="width:188pt;height:31.5pt" width="250">Doxorubicinol (DOXol)</td>
			<td class="xl20" style="width:122pt" width="162">Toronto Research Chemicals</td>
			<td class="xl20" style="width:89pt" width="119">D558020</td>
			<td class="xl21">Metabolite of DOX</td>
		</tr>
		<tr height="21" style="height:15.75pt">
			<td class="xl20" height="21" style="width:188pt;height:15.75pt" width="250">4-Methylumbelliferone sodium salt&#160;</td>
			<td class="xl20" style="width:122pt" width="162">Sigma-Aldrich</td>
			<td class="xl20" style="width:89pt" width="119">M1508</td>
			<td class="xl21">Internal standard</td>
		</tr>
		<tr height="21" style="height:15.75pt">
			<td class="xl20" height="21" style="width:188pt;height:15.75pt" width="250">Myristic Acid</td>
			<td class="xl20" style="width:122pt" width="162">Sigma-Aldrich</td>
			<td class="xl20" style="width:89pt" width="119">544-63-8&#160;&#160;</td>
			<td class="xl21">Materials for poly-lipid hybrid nanoparticles</td>
		</tr>
		<tr height="21" style="height:15.75pt">
			<td class="xl20" height="21" style="width:188pt;height:15.75pt" width="250">Polyoxyethylene (100) Stearate</td>
			<td class="xl20" style="width:122pt" width="162">Spectrum</td>
			<td class="xl20" style="width:89pt" width="119">M1402</td>
			<td class="xl21">Materials for poly-lipid hybrid nanoparticles</td>
		</tr>
		<tr height="21" style="height:15.75pt">
			<td class="xl20" height="21" style="width:188pt;height:15.75pt" width="250">Polyoxyethylene (40) Stearate</td>
			<td class="xl20" style="width:122pt" width="162">Sigma-Aldrich</td>
			<td class="xl20" style="width:89pt" width="119">P3440</td>
			<td class="xl21">Materials for poly-lipid hybrid nanoparticles</td>
		</tr>
		<tr height="21" style="height:15.75pt">
			<td class="xl20" height="21" style="width:188pt;height:15.75pt" width="250">Pluronic F68 (PF68)</td>
			<td class="xl20" style="width:122pt" width="162">BASF Corp.</td>
			<td class="xl20" style="width:89pt" width="119">9003-11-6</td>
			<td class="xl21">Materials for poly-lipid hybrid nanoparticles</td>
		</tr>
		<tr height="42" style="height:31.5pt">
			<td class="xl20" height="42" style="width:188pt;height:31.5pt" width="250">Ultrasonication (UP100H)</td>
			<td class="xl20" style="width:122pt" width="162">Hielscher, Ultrasound Technology</td>
			<td class="xl20" style="width:89pt" width="119">NA</td>
			<td class="xl21">Nanoparticle preparation</td>
		</tr>
		<tr height="21" style="height:15.75pt">
			<td class="xl20" height="21" style="width:188pt;height:15.75pt" width="250">Water Bath (ISOTEMP 3016HS)</td>
			<td class="xl20" style="width:122pt" width="162">Fisher Scientific</td>
			<td class="xl20" style="width:89pt" width="119">NA</td>
			<td class="xl21">Nanoparticle preparation</td>
		</tr>
		<tr height="105" style="height:78.75pt">
			<td class="xl20" height="105" style="width:188pt;height:78.75pt" width="250">Liposomal Doxorubicin&#160; (Caelyx)</td>
			<td class="xl20" style="width:122pt" width="162">Janssen</td>
			<td class="xl20" style="width:89pt" width="119">Purchased from the pharmacy Princess Margaret Hospital</td>
			<td class="xl21">Clinically-approved nanoparticle formulation&#160;</td>
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		<tr height="21" style="height:15.75pt">
			<td class="xl20" height="21" style="width:188pt;height:15.75pt" width="250">HPLC-graded Methanol</td>
			<td class="xl21">Caledon Chemicals</td>
			<td class="xl20" style="width:89pt" width="119">6701-7-40</td>
			<td class="xl21">HPLC mobile phase composition</td>
		</tr>
		<tr height="25" style="height:18.75pt">
			<td class="xl20" height="25" style="width:188pt;height:18.75pt" width="250">HPLC-graded H2O</td>
			<td class="xl21">Caledon Chemicals</td>
			<td class="xl20" style="width:89pt" width="119">8801-7-40</td>
			<td class="xl21">HPLC mobile phase composition</td>
		</tr>
		<tr height="21" style="height:15.75pt">
			<td class="xl20" height="21" style="width:188pt;height:15.75pt" width="250">HPLC-graded Acetonitrile&#160;</td>
			<td class="xl20" style="width:122pt" width="162">Caledon Chemicals</td>
			<td class="xl20" style="width:89pt" width="119">1401-7-40</td>
			<td class="xl21">HPLC mobile phase composition</td>
		</tr>
		<tr height="21" style="height:15.75pt">
			<td class="xl20" height="21" style="width:188pt;height:15.75pt" width="250">Trifluoroacetic Acid</td>
			<td class="xl20" style="width:122pt" width="162">Sigma-Aldrich</td>
			<td class="xl20" style="width:89pt" width="119">302031</td>
			<td class="xl21">HPLC mobile phase composition</td>
		</tr>
		<tr height="42" style="height:31.5pt">
			<td class="xl20" height="42" style="width:188pt;height:31.5pt" width="250">0.45 &#956;m Nylon Membrane Filter Paper</td>
			<td class="xl20" style="width:122pt" width="162">Whatman</td>
			<td class="xl20" style="width:89pt" width="119">WHA7404004</td>
			<td class="xl21">HPLC mobile phase preparation</td>
		</tr>
		<tr height="42" style="height:31.5pt">
			<td class="xl29" height="42" style="height:31.5pt">1cc Plastic Syringes</td>
			<td class="xl20" style="width:122pt" width="162">Becton, Dickinson and Company</td>
			<td class="xl20" style="width:89pt" width="119">2606-309659</td>
			<td class="xl21">Treatment injection</td>
		</tr>
		<tr height="42" style="height:31.5pt">
			<td class="xl29" height="42" style="height:31.5pt">5cc Plastic Syringes</td>
			<td class="xl20" style="width:122pt" width="162">Becton, Dickinson and Company</td>
			<td class="xl20" style="width:89pt" width="119">2608-309646</td>
			<td class="xl21">Tissue collections</td>
		</tr>
		<tr height="42" style="height:31.5pt">
			<td class="xl20" height="42" style="width:188pt;height:31.5pt" width="250">30G 1/2 Needles</td>
			<td class="xl20" style="width:122pt" width="162">Becton, Dickinson and Company</td>
			<td class="xl20" style="width:89pt" width="119">305106</td>
			<td class="xl21">Treatment injection</td>
		</tr>
		<tr height="42" style="height:31.5pt">
			<td class="xl20" height="42" style="width:188pt;height:31.5pt" width="250">25G 5/8 Needles</td>
			<td class="xl20" style="width:122pt" width="162">Becton, Dickinson and Company</td>
			<td class="xl20" style="width:89pt" width="119">305122</td>
			<td class="xl21">Tissue collections</td>
		</tr>
		<tr height="42" style="height:31.5pt">
			<td class="xl20" height="42" style="width:188pt;height:31.5pt" width="250">Sterile 0.9% Saline</td>
			<td class="xl20" style="width:122pt" width="162">Univeristy of Toronto House Brand</td>
			<td class="xl20" style="width:89pt" width="119">1011</td>
			<td class="xl21">Tissue perfusion</td>
		</tr>
		<tr height="22" style="height:16.5pt">
			<td class="xl20" height="22" style="width:188pt;height:16.5pt" width="250">13 ml Rounded-bottom conical tube&#160;</td>
			<td class="xl20" style="width:122pt" width="162">SARSTEDT</td>
			<td class="xl20" style="width:89pt" width="119">62.515.006</td>
			<td class="xl21">Prolyprolene, tissue homogenization</td>
		</tr>
		<tr height="23" style="height:17.25pt">
			<td class="xl30" height="23" style="height:17.25pt">Alpha Minimum Essential Medium (MEM)&#160;</td>
			<td class="xl27">Gibco</td>
			<td class="xl28" style="width:89pt" width="119">12571063</td>
			<td class="xl21">Cell medium</td>
		</tr>
		<tr height="22" style="height:16.5pt">
			<td class="xl20" height="22" style="width:188pt;height:16.5pt" width="250">1 x Phosphate Buffer Saline</td>
			<td class="xl20" style="width:122pt" width="162">Gibco</td>
			<td class="xl20" style="width:89pt" width="119">10010023</td>
			<td class="xl21">Tissue homogenization</td>
		</tr>
		<tr height="21" style="height:15.75pt">
			<td class="xl20" height="21" style="width:188pt;height:15.75pt" width="250">Triton X-100</td>
			<td class="xl20" style="width:122pt" width="162">Sigma-Aldrich</td>
			<td class="xl20" style="width:89pt" width="119">X100-100 ML</td>
			<td class="xl21">Tissue homogenization</td>
		</tr>
		<tr height="21" style="height:15.75pt">
			<td class="xl20" height="21" style="width:188pt;height:15.75pt" width="250">Formic acid</td>
			<td class="xl20" style="width:122pt" width="162">Caledon Chemicals</td>
			<td class="xl20" style="width:89pt" width="119">1/5/3840</td>
			<td class="xl21">Adjust pH for extraction solvent</td>
		</tr>
		<tr height="42" style="height:31.5pt">
			<td class="xl20" height="42" style="width:188pt;height:31.5pt" width="250">Sodium heparin sprayed plastic tubes</td>
			<td class="xl20" style="width:122pt" width="162">Becton, Dickinson and Company</td>
			<td class="xl20" style="width:89pt" width="119">367878</td>
			<td class="xl21">Blood collection</td>
		</tr>
		<tr height="21" style="height:15.75pt">
			<td class="xl20" height="21" style="width:188pt;height:15.75pt" width="250">Analytical Weigh Balance&#160;</td>
			<td class="xl20" style="width:122pt" width="162">Sartorius&#160;</td>
			<td class="xl21">CPA225D</td>
			<td class="xl21">NA</td>
		</tr>
		<tr height="21" style="height:15.75pt">
			<td class="xl20" height="21" style="width:188pt;height:15.75pt" width="250">pH meters&#160;</td>
			<td class="xl20" style="width:122pt" width="162">Fisher Scientific</td>
			<td class="xl26">13-637-671</td>
			<td class="xl21">accumet BASIC</td>
		</tr>
		<tr height="21" style="height:15.75pt">
			<td class="xl20" height="21" style="width:188pt;height:15.75pt" width="250">Vortex Mixter</td>
			<td class="xl20" style="width:122pt" width="162">Fisher Scientific</td>
			<td class="xl20" style="width:89pt" width="119">02-215-365</td>
			<td class="xl21">Vortexing samples at desired speed</td>
		</tr>
		<tr height="21" style="height:15.75pt">
			<td class="xl20" height="21" style="width:188pt;height:15.75pt" width="250">1.5 ml&#160; Microcentrifuge Tube</td>
			<td class="xl20" style="width:122pt" width="162">Fisherbrand</td>
			<td class="xl20" style="width:89pt" width="119">2043-05408129</td>
			<td class="xl21">Prolyprolene</td>
		</tr>
		<tr height="21" style="height:15.75pt">
			<td class="xl20" height="21" style="width:188pt;height:15.75pt" width="250">Model 1000 homogenizer</td>
			<td class="xl22">Fisher Scientific</td>
			<td class="xl20" style="width:89pt" width="119">08-451-672</td>
			<td class="xl21">Tissue homogenization</td>
		</tr>
		<tr height="21" style="height:15.75pt">
			<td class="xl20" height="21" style="width:188pt;height:15.75pt" width="250">Centrifuge 5702R</td>
			<td class="xl20" style="width:122pt" width="162">Eppendorf</td>
			<td class="xl20" style="width:89pt" width="119">5702R</td>
			<td class="xl21">Extraction preparation</td>
		</tr>
		<tr height="21" style="height:15.75pt">
			<td class="xl20" height="21" style="width:188pt;height:15.75pt" width="250">Heated Evaporator System</td>
			<td class="xl20" style="width:122pt" width="162">Glas-Col</td>
			<td class="xl20" style="width:89pt" width="119">NA</td>
			<td class="xl21">Sample reconstitution</td>
		</tr>
		<tr height="21" style="height:15.75pt">
			<td class="xl20" height="21" style="width:188pt;height:15.75pt" width="250">HPLC Screw Thread Vials</td>
			<td class="xl20" style="width:122pt" width="162">DIKMA</td>
			<td class="xl20" style="width:89pt" width="119">5320</td>
			<td class="xl21">HPLC sample injection</td>
		</tr>
		<tr height="42" style="height:31.5pt">
			<td class="xl20" height="42" style="width:188pt;height:31.5pt" width="250">HPLC Screw Caps with PTFE White Silicone Septa</td>
			<td class="xl20" style="width:122pt" width="162">DIKMA</td>
			<td class="xl20" style="width:89pt" width="119">5325</td>
			<td class="xl21">HPLC sample injection</td>
		</tr>
		<tr height="21" style="height:15.75pt">
			<td class="xl20" height="21" style="width:188pt;height:15.75pt" width="250">HPLC Polypropylene Insert&#160;&#160;</td>
			<td class="xl20" style="width:122pt" width="162">Agilent Technologies</td>
			<td class="xl20" style="width:89pt" width="119">5182-0549</td>
			<td class="xl21">Maximum volume 250 &#956;l, HPLC sample injection</td>
		</tr>
		<tr height="25" style="height:18.75pt">
			<td class="xl20" height="25" style="width:188pt;height:18.75pt" width="250">Xbridge C18 Column</td>
			<td class="xl23">Waters Corporation</td>
			<td class="xl20" style="width:89pt" width="119">186003117</td>
			<td class="xl21">Drug analysis</td>
		</tr>
		<tr height="21" style="height:15.75pt">
			<td class="xl20" height="21" style="width:188pt;height:15.75pt" width="250">Gradient pump&#160;</td>
			<td class="xl23">Waters Corporation</td>
			<td class="xl20" style="width:89pt" width="119">W600</td>
			<td class="xl21">Drug analysis</td>
		</tr>
		<tr height="21" style="height:15.75pt">
			<td class="xl20" height="21" style="width:188pt;height:15.75pt" width="250">Auto-sampler</td>
			<td class="xl23">Waters Corporation</td>
			<td class="xl20" style="width:89pt" width="119">W2707</td>
			<td class="xl21">Drug analysis</td>
		</tr>
		<tr height="21" style="height:15.75pt">
			<td class="xl20" height="21" style="width:188pt;height:15.75pt" width="250">Photodiode array detector&#160;</td>
			<td class="xl23">Waters Corporation</td>
			<td class="xl20" style="width:89pt" width="119">W2998</td>
			<td class="xl21">Drug analysis</td>
		</tr>
		<tr height="21" style="height:15.75pt">
			<td class="xl20" height="21" style="width:188pt;height:15.75pt" width="250">Multi &#955; fluoresence detector&#160;</td>
			<td class="xl23">Waters Corporation</td>
			<td class="xl20" style="width:89pt" width="119">W2475</td>
			<td class="xl21">Drug analysis</td>
		</tr>
		<tr height="21" style="height:15.75pt">
			<td class="xl20" height="21" style="width:188pt;height:15.75pt" width="250">EMPOWER 2</td>
			<td class="xl23">Waters Corporation</td>
			<td class="xl20" style="width:89pt" width="119">NA</td>
			<td class="xl21">Data analysis software</td>
		</tr>
		<tr height="21" style="height:15.75pt">
			<td class="xl20" height="21" style="width:188pt;height:15.75pt" width="250">Scientist</td>
			<td class="xl20" style="width:122pt" width="162">Micromath</td>
			<td class="xl20" style="width:89pt" width="119">NA</td>
			<td class="xl21">Pharmacokinetic analysis</td>
		</tr>
		<tr height="21" style="height:15.75pt">
			<td class="xl20" height="21" style="width:188pt;height:15.75pt" width="250">Female Balb/c Mice</td>
			<td class="xl20" style="width:122pt" width="162">Jackson Laboratory</td>
			<td class="xl20" style="width:89pt" width="119">001026</td>
			<td class="xl21">In vivo</td>
		</tr>
		<tr height="63" style="height:47.25pt">
			<td class="xl20" height="63" style="width:188pt;height:47.25pt" width="250">EMT6/WT Breast Cancer Cells</td>
			<td class="xl20" style="width:122pt" width="162">Provided by Dr. Ian Tannock; Ontario Cancer Institute</td>
			<td class="xl20" style="width:89pt" width="119">NA</td>
			<td class="xl21">In vivo</td>
		</tr>
	</tbody>
</table>

sample extraction and simultaneous chromatographic quantitation of doxorubicin and mitomycin c following drug combination delivery in nanoparticles to tumor-bearing mice

联合化疗常用于肿瘤治疗的临床;然而, 与正常组织相关的不良反应可能会限制其治疗效果。纳米药物组合已被证明可以缓解问题的免费药物联合治疗。我们以前的研究表明, 两种抗癌药物, 阿霉素 (DOX) 和丝裂霉素 C (MMC) 的结合, 产生了对小鼠和人乳腺癌细胞的协同作用体外。DOX 和 MMC co-loaded 聚合物脂质杂交纳米颗粒 (DMPLN) 绕过各种外排转运泵, 赋予多药耐药性, 并证明了乳腺肿瘤模型的增强功效。与传统的溶液形式相比, 这种 DMPLN 的优越功效归因于 DOX 和 MMC 的同步药代动力学, 以及 nanocarrier PLN 所启用的肿瘤细胞内的细胞药物生物利用度的提高。
为了评价 co-administered DOX 和 MMC 在自由溶液和纳米颗粒中的药代动力学和生物分布, 采用反相高效液相色谱 (HPLC) 的简单高效的药物分析方法是开发.与以前报告的方法, 分别分析 DOX 或 mmc 在等离子体中, 这种新的 HPLC 法可以同时定量 DOX, mmc 和主要有氧 DOX 代谢物, doxorubicinol (DOXol), 在各种生物矩阵 (例如,全血, 乳腺肿瘤和心脏)。采用双荧光和紫外线吸收探针 4-伞形 (4 亩) 作为一个内部标准 (行列) one-step 检测多种药物分析不同的检测波长。该方法成功地应用于原位乳腺肿瘤小鼠模型中的全血和不同组织中纳米颗粒和溶液方法的 DOX 和 MMC 的浓度测定。所提出的分析方法是临床前分析药物组合纳米分娩的有效工具。

两种抗癌药物, DOX 和 MMC, 以及 DOX 代谢物, DOXol, 同时检测没有任何生物干扰在相同的应用梯度 HPLC 条件下使用4亩作为行列的荧光和紫外线探测器。DOX, mmc, DOXol 和4亩分离从彼此的保留时间为5.7 分钟的 MMC, 10.4 分钟 DOXol, 10.9 分钟4亩, 11.1 分钟 DOX (图 2)。全血和各种组织中的每种药物都显示了相关系数的浓度线性 (R2), 范围从0.98 到 1.00 (<...

Watch this Scientific Journal Video about Sample Extraction and Simultaneous Chromatographic Quantitation of Doxorubicin and Mitomycin C Following Drug Combination Delivery in Nanoparticles to Tumor-b

Sample Extraction and Simultaneous Chromatographic Quantitation of Doxorubicin and Mitomycin C Following Drug Combination Delivery in Nanoparticles to Tumor-bearing Mice

纳米颗粒对荷瘤小鼠药相结合的样品提取及同时色谱定量分析

该协议描述了一个高效和方便的分析过程中的样品提取和同时测定多药, 阿霉素 (DOX), 丝裂霉 C (MMC) 和心脏毒性 DOX 代谢物, doxorubicinol (DOXol), 在生物样品的临床前乳腺癌模型治疗的纳米颗粒制剂的协同药物组合。

Combination chemotherapy is frequently used in the clinic for cancer treatment; however, associated adverse effects to normal tissue may limit its ...

Research

JoVE Journal

Cancer Research

Using RNA-sequencing to Detect Novel Splice Variants Related to Drug Resistance in In Vitro Cancer Models

Using RNA-sequencing to Detect Novel Splice Variants Related to Drug Resistance in In Vitro Cancer Models

利用RNA测序来检测新剪接变异体在相关耐药<em&gt;体外</em&gt;癌症模型

Drug resistance remains a major problem in the treatment of cancer for both hematological malignancies and solid tumors. Intrinsic or acquired resistance ...

科研

癌症研究

The Colon-26 Carcinoma Tumor-bearing Mouse as a Model for the Study of Cancer Cachexia

结肠-26癌荷瘤小鼠为癌症恶病质的研究模型

Cancer cachexia is the progressive loss of skeletal muscle mass and adipose tissue, negative nitrogen balance, anorexia, fatigue, inflammation, and ...

In Vivo EPR Assessment of pH, pO2, Redox Status, and Concentrations of Phosphate and Glutathione in the Tumor Microenvironment

In Vivo EPR Assessment of pH, pO2, Redox Status, and Concentrations of Phosphate and Glutathione in the Tumor Microenvironment

体内在肿瘤微环境中 pH 值、 pO2、氧化还原状态、磷酸盐和谷胱甘肽浓度的 EPR 评价

This protocol demonstrates the capability of low-field electron paramagnetic resonance (EPR)-based techniques in combination with functional paramagnetic ...

Methods for Evaluating the Role of c-Fos and Dusp1 in Oncogene Dependence

c-fos 和 dusp1 在癌基因依赖性中的作用评价方法

The demonstration of tyrosine kinase inhibitors (TKIs) in treating chronic myeloid leukemia (CML) has heralded a new era in cancer therapeutics. However, ...

Potentiation of Anticancer Antibody Efficacy by Antineoplastic Drugs: Detection of Antibody-drug Synergism Using the Combination Index Equation

抗肿瘤药物对抗癌抗体疗效的潜力: 用组合指数方程检测抗体-药物协同作用

Potentiation of hostile monoclonal antibodies (mAb) by chemotherapeutic agents constitutes a valuable strategy for designing effective and safer therapy ...

Transfer of Manipulated Tumor-associated Neutrophils into Tumor-Bearing Mice to Study their Angiogenic Potential In Vivo

将操纵的肿瘤相关中性粒细胞转移到肿瘤携带小鼠中,以研究其血管生成潜力在Vivo

The contribution of neutrophils to the regulation of tumorigenesis is getting increased attention. These cells are heterogeneous, and depending on the ...

In Vivo Imaging and Quantitation of the Host Angiogenic Response in Zebrafish Tumor Xenografts

在斑马鱼肿瘤异种移植物中宿主血管反应的Vivo成像和定量

Tumor angiogenesis is a key target of anti-cancer therapy and this method has been developed to provide a new model to study this process in vivo. A ...

Evaluation of the In vivo Antitumor Activity of Polyanhydride IL-1&#945; Nanoparticles

Evaluation of the In vivo Antitumor Activity of Polyanhydride IL-1ÃƒÅ½Ã‚Â± Nanoparticles

聚酐IL-1α纳米颗粒 体内抗肿瘤 活性评价

Cytokine therapy is a promising immunotherapeutic strategy that can produce robust antitumor immune responses in cancer patients. The proinflammatory ...

Exploring Mitochondrial Energy Metabolism of Single 3D Microtissue Spheroids Using Extracellular Flux Analysis

Three-dimensional (3D) cellular aggregates, termed spheroids, have become the forefront of in vitro cell culture in recent years. In contrast to culturing ...

Simultaneous Imaging and Flow-Cytometry-based Detection of Multiple Fluorescent Senescence Markers in Therapy-Induced Senescent Cancer Cells

基于同步成像和流式细胞术检测治疗诱导的衰老癌细胞中的多种荧光衰老标志物

Chemotherapeutic drugs can induce irreparable DNA damage in cancer cells, leading to apoptosis or premature senescence. Unlike apoptotic cell death, ...